Riboswitch helps bacteria toss out toxic fluoride.

Bacteria, such as streptococcus, use an RNA switch to turn on genes that fight off toxic fluoride.

Since the early 1950s, fluoride has been added to toothpaste, mouthwash, and water to strengthen tooth enamel and prevent tooth decay by killing bacteria. Now, research by HHMI investigator Ronald R. Breaker shows how bacteria that live inside the mouth respond to this toxic ion.

Breaker’s lab group at Yale University studies a type of noncoding RNA, called a riboswitch, that helps turn genes on and off. Riboswitches are attached to the genes they regulate; if a gene is involved in the production of a certain compound, the riboswitch usually is sensitive to that compound. If the level of the compound gets too high or too low, the riboswitch can cause more or less of it to be made.

Recently, Breaker and his colleagues discovered a riboswitch attached to several genes with a diverse set of functions. Curious about the riboswitch’s job, the scientists put the RNA in a test tube and added different compounds, observing whether the substances bound to the riboswitch. They worked through a long list of chemicals before accidentally stumbling upon fluoride—the ion was a contaminant in one sample they were testing.

Once the team learned their riboswitch interacted with fluoride, they determined that some of the genes controlled by the RNA are involved in removing fluoride from a cell. Breaker explains that when fluoride builds up to toxic levels in a cell, a riboswitch binds to fluoride and turns on genes that can overcome its effects by transporting it out of the cell.

Because genes associated with fluoride-sensitive riboswitches are found in many types of bacteria, fungi, and plants, the research team concluded that these RNAs and the genes they control may represent components of an ancient system that cells have evolved to deal with toxic levels of this ion. The researchers published their findings January 13, 2012, in Science.

“Our data not only help explain how cells fight the toxicity of fluoride, the results also give us a sense of how we might enhance the antimicrobial properties of fluoride,” says Breaker. For example, the researchers showed that deleting the fluoride channel makes cells 200 times more sensitive to fluoride.

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